He pitched for the Hiroshima Toyo Carp in Nippon Professional Baseball (NPB), and the Colorado Rockies, Kansas City Royals, Boston Red Sox, San Francisco Giants, New York Mets, and Baltimore Orioles of Major League Baseball (MLB).

[1] The winning bid was placed by the New York Yankees, who signed him on March 5, 2003, and assigned him to their minor league system.

After he had a 2–8 record, a 5.21 earned run average (ERA), 21 strikeouts, and 21+1⁄3 innings pitched in 14 starts, he was promoted to the Trenton Thunder of the Double-A Eastern League.

With the Thunder, he had a 1–1 record, a 1.69 ERA, 21 strikeouts, and 21+1⁄3 innings pitched in four games (three starts), and this earned him a promotion to the Columbus Clippers of the triple-A International League.

He finished his first minor league season with a 3–10 record, a 4.43 ERA, 96 strikeouts, and 101+2⁄3 innings pitched in 20 games (18 starts).

[6][7] On August 17, he allowed just two hits in a 4–1 complete game victory over the Norwich Navigators while setting a team record by retiring the last 24 hitters he faced.

His combined minor league totals were a 4–9 record, a 5.14 ERA, two complete games, 145 strikeouts, and 133 innings pitched in 22 starts.

After he had a 1–3 record, a 5.33 ERA, 23 strikeouts, and 25+1⁄3 innings pitched in six starts for the Clippers, he was demoted to Trenton for the second year in a row.

[6] On July 28, the Yankees traded Ramírez and Eduardo Sierra to the Colorado Rockies for Shawn Chacón.

[6] After throwing a scoreless inning for Colorado Springs, he was called up by the Rockies on April 12 when Mike DeJean was placed on the disabled list.

[10] Five days later, he singled against Chan Ho Park in his first major league at bat in a 13–4 loss to the San Diego Padres.

[7] Ramírez's streak ended on May 15, when he allowed three runs in 1⁄3 of an inning and got his first career loss against the Los Angeles Dodgers, who won 5–4.

[15] On September 30, in his final game of the season, he pitched 1+2⁄3 scoreless innings and got the win in a 14-inning, 11–9 victory over the Chicago Cubs.

[23] A week later, he was recalled when Willy Taveras was placed on the disabled list,[24] but he was returned to the minors two days later after appearing in one game.

[7] On September 8, he was called up and placed on the 60-day disabled list with elbow inflammation so the Rockies could put Josh Newman on their roster.

[6] Ramírez was traded to the Kansas City Royals on March 26, 2008, for a player to be named later (Jorge de la Rosa).

[29] On July 20, he got his first win since May 21 of the previous year in an 8–7 victory over the Chicago White Sox, despite blowing the lead by giving up two runs in 1+1⁄3 innings.

He was one of three major league pitchers to give up two or fewer home runs in over 70 innings (along with Roy Corcoran and Jason Grilli), and he was one of the American League (AL) pitchers to have an ERA under 3.00 with at least 70 innings pitched and 70 strikeouts (along with Francisco Rodríguez and Matt Thornton).

[34] On April 24, 2009, he pitched a scoreless inning for the Red Sox and earned the win in an 11-inning 5–4 victory over the New York Yankees.

In Game 1 of the American League Division Series (ALDS), he gave up two runs without recording an out in his only playoff appearance, a 5–0 loss to the Angels.

[40] On April 27, 2010, Ramírez got his first save since 2008 in a 2–1 win over the Baltimore Orioles, since Red Sox manager Terry Francona wanted to rest closer Jonathan Papelbon.

[43] Ramírez had an 0–3 record, a 4.46 ERA, 2 saves, 31 strikeouts, and 41+2⁄3 innings pitched with the Red Sox through July 31, the trade deadline.

[45] He got a save against the Diamondbacks on September 30, since Giants' manager Bruce Bochy wanted to rest closer Brian Wilson, in a 4–1 victory.

[46] Ramírez posted a 1–0 record, an 0.67 ERA, 15 strikeouts, and 27 innings pitched in 25 games for the Giants as they won the National League (NL) West and reached the playoffs for the first time since 2003.

[47] In Game 2 of the NL Championship Series, Ramírez gave up two runs in 1⁄3 of an inning as the Giants lost 6–1 to the Phillies.

[52] Ramírez earned a save on April 6, 2011, by pitching 1⁄3 of an inning to escape a bases-loaded situation in the Giants' 8–4 win over the Padres.

[55] On August 5, in an eventual 9–2 loss to Philadelphia, Ramírez hit Shane Victorino with a pitch, and a brawl started.

Ramírez signed a minor league contract with the Giants in 2013, but he was released on March 22 after posting an 11.25 ERA in spring training.

On July 1, 2013 Ramirez signed a minor league deal with the Tampa Bay Rays organization.

[7] He often donates baseball equipment to children who need it, and in 2006 the Rockies recognized him for this by making him their Roberto Clemente Award nominee.